Epigenetic modification of PKMζ rescues aging-related cognitive impairment
Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial mole...
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Nature Publishing Group
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772003/ |
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pubmed-4772003 |
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pubmed-47720032016-03-07 Epigenetic modification of PKMζ rescues aging-related cognitive impairment Chen, Chen Meng, Shi-Qiu Xue, Yan-Xue Han, Ying Sun, Cheng-Yu Deng, Jia-Hui Chen, Na Bao, Yan-Ping Zhang, Fei-Long Cao, Lin-Lin Zhu, Wei-Guo Shi, Jie Song, Wei-Hong Lu, Lin Article Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue. Nature Publishing Group 2016-03-01 /pmc/articles/PMC4772003/ /pubmed/26926225 http://dx.doi.org/10.1038/srep22096 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Chen, Chen Meng, Shi-Qiu Xue, Yan-Xue Han, Ying Sun, Cheng-Yu Deng, Jia-Hui Chen, Na Bao, Yan-Ping Zhang, Fei-Long Cao, Lin-Lin Zhu, Wei-Guo Shi, Jie Song, Wei-Hong Lu, Lin |
| spellingShingle |
Chen, Chen Meng, Shi-Qiu Xue, Yan-Xue Han, Ying Sun, Cheng-Yu Deng, Jia-Hui Chen, Na Bao, Yan-Ping Zhang, Fei-Long Cao, Lin-Lin Zhu, Wei-Guo Shi, Jie Song, Wei-Hong Lu, Lin Epigenetic modification of PKMζ rescues aging-related cognitive impairment |
| author_facet |
Chen, Chen Meng, Shi-Qiu Xue, Yan-Xue Han, Ying Sun, Cheng-Yu Deng, Jia-Hui Chen, Na Bao, Yan-Ping Zhang, Fei-Long Cao, Lin-Lin Zhu, Wei-Guo Shi, Jie Song, Wei-Hong Lu, Lin |
| author_sort |
Chen, Chen |
| title |
Epigenetic modification of PKMζ rescues aging-related cognitive impairment |
| title_short |
Epigenetic modification of PKMζ rescues aging-related cognitive impairment |
| title_full |
Epigenetic modification of PKMζ rescues aging-related cognitive impairment |
| title_fullStr |
Epigenetic modification of PKMζ rescues aging-related cognitive impairment |
| title_full_unstemmed |
Epigenetic modification of PKMζ rescues aging-related cognitive impairment |
| title_sort |
epigenetic modification of pkmζ rescues aging-related cognitive impairment |
| description |
Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue. |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4772003/ |
| _version_ |
1613545058165850112 |